Improving Atrial Fibrillation Therapy

While AF most often occurs in the setting of atrial disease, current assessment and treatment of patients with AF does not focus on the extent of the atrial myopathy that serves as the substrate for this arrhythmia. Atrial myopathy, in particular atrial fibrosis, may initiate a vicious cycle in which atrial myopathy leads to AF, which in turn leads to a worsening myopathy. Various techniques, including ECG, plasma biomarkers, electroanatomical voltage mapping, echocardiography, and cardiac MRI, can help to identify and quantify aspects of the atrial myopathy. Current therapies, such as catheter ablation, do not directly address the underlying atrial myopathy. There is emerging research showing that by targeting this myopathy we can help decrease the occurrence and burden of AF.

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“…[ 166 ] Other potential targets of gene therapy include modification of ion channels, gap junctions, autonomic innervation, and fibrosis. [ 167 ]…”

Section: Guiding Therapies To Target Fibrosismentioning

confidence: 99%

Atrial Myopathy Underlying Atrial Fibrillation

Rivner

Mitrani

Goldberger

2020

Arrhythmia &Amp; Electrophysiology Review

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“…Thus, IGFBP2 and IGFBP3 might bind and regulate the functions of IGFs through IGF transport and uptake by IGFBPs pathway, and then affected the susceptibility of AF [20]. To date, microRNAs have been regarded as possible targets for gene therapy in AF [24]. In the study, hsa-miR-197-3p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-340-5p and hsa-miR-9-5p targeting IGFBP3 were predicted and might be potential biomarkers of AF.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Crucial Genes in Atrial Fibrillation: A Bioinformatic Analysis

Zhang

Huang

Wang

et al. 2020

Preprint

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Abstract Background Atrial fibrillation (AF) is at least partially heritable, affecting 2-3% of the population in Europe and the USA. However, a substantial proportion of heritability is still lacking. In the present study, we aim to identify potential crucial genes associated with AF through bioinformatic analyses of public datasets. Methods Microarray data sets of GSE115574, GSE31821, GSE79768, GSE41177 and GSE14975 from the Gene Expression Omnibus (GEO) database were retrieved. After merging all microarray data and adjusting batch effect, differentially expressed genes (DEGs) were identified. Functional enrichment analyses based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource, Gene Set Enrichment Analysis (GSEA), Reactome Pathway Database and Disease Ontology (DO) were carried out. Protein-protein interaction (PPI) network was constructed using the STRING database. Combined with aforementioned significant bioinformatics information, potential crucial genes were subsequently selected. The comparative toxicogenomics database (CTD) was carried out to explore the interaction between potential crucial genes and AF. Result We identified 27 of DEGs with gene expression fold change (FC) ≥ 1.5 or ≤ 2/3 (|log2 FC| ≥ 0.58) and 5 with FC ≥ 2 or ≤ 0.5 (|log2 FC| ≥ 1) of AF patients compared with sinus rhythm controls. The most significantly enriched pathway was regulation of insulin-like growth factor transport and uptake by insulin-like growth factor binding proteins. IGFBP2, C1orf105, FHL2, CHGB, ATP1B4, IGFBP3, SLC26A9, CXCR4 and HTR2B were considered the potential crucial genes. CTD showed CXCR4, IGFBP2, IGFBP3 and FHL2 had higher scores with AF. Conclusions The 9 potential crucial genes, especially CXCR4, IGFBP2, IGFBP3 and FHL2 , may be associated with risk of AF. Our study provided new insights of AF into genetics, molecular pathogenesis and new therapeutic targets.

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“…Both of these mechanisms are dependent on electrical and structural remodeling, autonomic nerve remodeling and Ca 2+ -handling abnormalities. 74 Electrical remodeling is typically characterized by shortening of the atrial action potential duration (APD) through a decrease in the L-type Ca 2+ current and an increase in the inward-rectifier current (I K1 ), and the emergence of constitutively active acetylcholine induced potassium current (I KACh ). 2 Structural remodeling results in left atrial enlargement, atrial fibrosis, and gap junction remodeling, culminating as slow and heterogeneous conduction.…”

Section: Targets For Gene Therapymentioning

confidence: 99%

Recent Advances in Gene Therapy for Atrial Fibrillation

Yoo¹,

Geist²,

Pfenniger³

et al. 2021

Preprint

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Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments for AF are suboptimal as they are not targeting the molecular mechanisms underlying AF. In this regard, gene therapy is emerging as a promising approach for mechanism-based treatment of AF. In this review, we summarize recent advances and challenges in gene therapy for this important cardiovascular disease.

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Improving Atrial Fibrillation Therapy

Cited by 24 publications

References 54 publications

Atrial Myopathy Underlying Atrial Fibrillation

Atrial Myopathy Underlying Atrial Fibrillation

Identification of Potential Crucial Genes in Atrial Fibrillation: A Bioinformatic Analysis

Recent Advances in Gene Therapy for Atrial Fibrillation

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